This invention concerns a vascular prosthesis having a luminal surface with anti-thrombogenic characteristics and the method of preparation thereof. More particularly the invention concerns a method for enhancing the attachment and growth of endothelial cells on a matrix, such as a vascular prosthesis and a synthetic vascular prosthesis having a luminal surface, i.e. the blood contacting surface which is provided with an enhancing agent for the attachment of endothelial cells.
Due to continuously improving surgical techniques, the implantation of prosthetic vascular grafts is increasing. However, the clinical usefulness of synthetic vascular prostheses for vascular reconstruction is limited by the tendency of such grafts to thrombogenicity.
An endothelial cell lining within a graft is believed to provide a non-thrombogenic surface. According to recent investigations by Graham et al, Arch. Surg. 115 1289 (1980) and Surgery 91, 550 (1982) and Burkel et al, J. Surg. Res. 30, 305 (1981), improvement in the development of an endothelial lining in dacron and in polytetrafluoroethylene vascular grafts is obtained by seeding the prosthesis with endothelial cells prior to implantation.
It is well known that the substrate is critical to the growth and proliferation of cells. Among the many materials which have been investigated for effectiveness as cell substrates are collage and fibronectin, components of the extracellular matrix and the intact extracellular matrix. The ability of these proteins to promote cell adhesion, growth and motility have been studied in particular by Postlewaite et al, Proc. Natl. Acad. Sci. USA 75, 871 (1978); Kleinman et al, J. Cell Biol. 88, 473 (1981); Seppa et al, Cell. Biol. 5, 813 (1981); Ali et al, Cell. 14, 439 (1978); Klebe, Nature 250, 248 (1974); Gospodarowicz et al, Proc. Natl. Acad. Sci. USA 77, 4094 (1980) and Klebe et al, J. Cell. Physiol. 109, 481 (1981).
The properties, structure and composition of elastin, another protein of the vascular wall have also been investigated extensively, for example, by Partridge et al, Biochem. J. 61, 11 (1955) and Clearly et al, Exp. Mol. Pathol 28, 227 (1978). More recently, the biosynthesis of elastin by ligamentum nuchae fibroblast has been reported by Mecham et al, J. Cell. Biol. 90, 332 (1981); Senior et al, J. Clin. Invest. 66, 859 (1980) have disclosed that elastin derived peptides, produced by digesting elastin with human neutrophil elastase, are chemotactic for human inflammatory cells and the preparation of an elastomer by cross linking a synthetic polytetrapeptide similar to elastin sequences (but not containing desmosines) has been disclosed by Urry et al, J. Biomed. Mat. Res. 16, 11 (1982).
Studies concerning the interaction of endothelial and vascular smooth muscle cells have been reported by Karnovsky Amer. J. Pathol. 105, 200 (1981) and Haudenschild et al, Lab. Inves. 41, 407 (1979).
However, these studies have not yet led to improvements needed in the performance of vascular prostheses, particularly for small vessel prostheses.